title: Ifit1 inhibits Japanese encephalitis virus replication through binding to 5' capped 2'-O unmethylated RNA.
abstract: The interferon-inducible protein with tetratricopeptide (IFIT) family proteins inhibit replication of some viruses by recognizing several types of RNAs, including 5'-triphosphate RNA and 5' capped 2'-O unmethylated mRNA. However, it remains unclear how IFITs inhibit replication of some viruses through recognition of RNA. Here, we analyzed the mechanisms by which Ifit1 exerts antiviral responses. Replication of a Japanese encephalitis virus (JEV) 2'-O methyltransferase (MTase) mutant was markedly enhanced in mouse embryonic fibroblasts and macrophages lacking Ifit1. Ifit1 bound 5'-triphosphate RNA but more preferentially associated with 5' capped 2'-O unmethylated mRNA. Ifit1 inhibited the translation of mRNA and thereby restricted the replication of JEV mutated in 2'-O MTase. Thus, Ifit1 inhibits replication of MTase-defective JEV by inhibiting mRNA translation through direct binding to mRNA 5' structures.
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Kimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katoh
authors.forename: Hisako
authors.initials: H
authors.lastname: Kayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Saiga
authors.forename: Megumi
authors.initials: M
authors.lastname: Okuyama
authors.forename: Toru
authors.initials: T
authors.lastname: Okamoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Umemoto
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism*; D004664:Encephalitis Virus, Japanese / Q000276:immunology / Q000502:physiology*; D005347:Fibroblasts / Q000821:virology; D054884:Host-Pathogen Interactions; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins; D014779:Virus Replication
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C092573:Ifit1 protein, mouse; D012367:RNA, Viral; D016601:RNA-Binding Proteins